Tracking the Effect of Cathodal Transcranial Direct Current Stimulation on Cortical Excitability and Connectivity by Means of TMS-EEG.

Erica Varoli,Alessandra Vergallito,Nadia Bolognini,Giuseppe Vallar,Giulia C Mattavelli,Leonor J Romero Lauro,Alessia Gallucci,Mario Rosanova,Lilia D Mauro,Alberto Pisoni

doi:10.3389/fnins.2018.00319

Abstract

Transcranial direct current stimulation (tDCS) is increasingly used in both research and therapeutic settings, but its precise mechanisms remain largely unknown. At a neuronal level, tDCS modulates cortical excitability by shifting the resting membrane potential in a polarity-dependent way: anodal stimulation increases the spontaneous firing rate, while cathodal decreases it. However, the neurophysiological underpinnings of anodal/cathodal tDCS seem to be different, as well as their behavioral effect, in particular when high order areas are involved, compared to when motor or sensory brain areas are targeted. Previously, we investigated the effect of anodal tDCS on cortical excitability, by means of a combination of Transcranial Magnetic Stimulation (TMS) and Electroencephalography (EEG). Results showed a diffuse rise of cortical excitability in a bilateral fronto-parietal network. In the present study, we tested, with the same paradigm, the effect of cathodal tDCS. Single pulse TMS was delivered over the left posterior parietal cortex (PPC), before, during, and after 10 min of cathodal or sham tDCS over the right PPC, while recording HD-EEG. Indexes of global and local cortical excitability were obtained both at sensors and cortical sources level. At sensors, global and local mean field power (GMFP and LMFP) were computed for three temporal windows (0–50, 50–100, and 100–150 ms), on all channels (GMFP), and in four different clusters of electrodes (LMFP, left and right, in frontal and parietal regions). After source reconstruction, Significant Current Density was computed at the global level, and for four Broadmann's areas (left/right BA 6 and 7). Both sensors and cortical sources results converge in showing no differences during and after cathodal tDCS compared to pre-stimulation sessions, both at global and local level. The same holds for sham tDCS. These data highlight an asymmetric impact of anodal and cathodal stimulation on cortical excitability, with a diffuse effect of anodal and no effect of cathodal tDCS over the parietal cortex. These results are consistent with the current literature: while anodal-excitatory and cathodal-inhibitory effects are well-established in the sensory and motor domains, both at physiological and behavioral levels, results for cathodal stimulation are more controversial for modulation of exitability of higher order areas.

Highlights

TDCS is one of the most used non-invasive brain stimulation techniques, there are relatively few studies addressing the mechanisms underlying its action
The synaptic activity induced by tDCS increases Ca2+ intracellular amount, affecting calcium and sodium membrane channels (Islam et al, 1995), and it is dependent on enhanced brain-derived neurotrophic factor (BDNF) secretion and TrkBactivation (Fritsch et al, 2010)
LMFP Analyses run on LMFP values did not support any effect of cathodal tDCS in any of the considered clusters of electrodes

Summary

Introduction

TDCS is one of the most used non-invasive brain stimulation techniques, there are relatively few studies addressing the mechanisms underlying its action (for a review see Stagg and Nitsche, 2011; Medeiros et al, 2012). When the duration of the stimulation exceeds 5 min, tDCS can induce long-lasting aftereffects, presumably deriving from changes in synaptic strength. These after-effects are dependent upon continuous protein synthesis during stimulation (Gartside, 1968), likely mediated by mechanisms such as Long-Term Potentiation and Depression (LTP and LTD; Hattori et al, 1990; Moriwaki, 1991; Liebetanz et al, 2002; Fritsch et al, 2010; Ranieri et al, 2012; Rohan et al, 2015). The synaptic activity induced by tDCS increases Ca2+ intracellular amount, affecting calcium and sodium membrane channels (Islam et al, 1995), and it is dependent on enhanced brain-derived neurotrophic factor (BDNF) secretion and TrkBactivation (Fritsch et al, 2010)

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Conclusion